The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography (EEG), magnetoencephalography (MEG), electromyography (EMG), and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of tic, psychogenic movement disorders, tremor and restless legs syndrome. [unreadable] We have been approaching the physiology of tics in several ways. Tourette syndrome patients report "premonitory urge" and other sensory abnormalities associated with the presence of tics. Using MEG, we investigated trigeminal somatosensory evoked responses in order to investigate possibilities of decreased habituation to sensation and network abnormalities which may account for the involvement of sensory symptoms in tics. Our preliminary results suggest that patients may not habituate normally to repetitive sensations. We have also been investigating the nature of urge. We performed an fMRI study in 18 healthy volunteers looking at the urge when naive subjects viewed an actor yawning, along with other control actions. The main area of activation was in the ventromedial prefrontal cortex. [unreadable] The pathophysiology of psychogenic movement disorders (PMD) is very poorly understood. We are studying the mechanisms underlying these disorders using cognitive tasks, neurophysiological testing, psychiatric measures, and functional imaging. The functional imaging study is an fMRI comparison of patients with tremor, and preliminary results show abnormal activation in dorsolateral prefrontal cortex. [unreadable] New treatments are needed for essential tremor. One promising agent is 1-octanol which we continue to develop. We are currently working to characterize this drug?s pharmacokinetics and comparing the efficacy of two different formulations in a dose escalation and cross-over study in patients with ET. In addition to characterizing the pharmacokinetics of 1-octanol, we are testing its efficacy in a double-blind placebo-controlled trial in patients with essential tremor. We are also collecting families with essential tremor looking for possible genetic abnormalities, and in several families found an area suggestive of genetic linkage on chromosome 6 and 11. [unreadable] We completed a study on restless legs syndrome (RLS) using an auditory and tactile prepulse with the blink reflex. Preliminary results show that there is decreased inhibition during a tactile prepulse in patients compared to controls. This finding suggests an abnormality in the spinal cord circuitry of RLS patients.